MiR-16-5p is frequently down-regulated in astrocytic gliomas and modulates glioma cell proliferation, apoptosis and response to cytotoxic therapy.

AIMS: Aberrant expression of microRNAs (miRNAs) is frequent in various cancers including gliomas. We aimed to characterize the role of miR-16-5p as a candidate tumour suppressor miRNA in gliomas. METHODS: Real-time PCR-based approaches were used for miRNA and mRNA expression profiling of glioma and non-neoplastic brain tissues as well as glioma cell lines. Protein levels were determined by Western blotting. In vitro analyses were performed following overexpression of miR-16-5p, trichostatin A (TSA) treatment, and siRNA-mediated knock-down of HDAC3 in glioma cells. Effects of miR-16-5p on glioma cell viability, apoptosis and response to irradiation and temozolomide (TMZ) were assessed. RESULTS: Expression of miR-16-5p was reduced relative to control brain tissue in isocitrate dehydrogenase (IDH)-mutant astrocytomas of World Health Organization (WHO) grades II, III and IV, and a subset of IDH-wildtype glioblastomas WHO grade IV. MiR-16-5p expression was lower in IDH-mutant than in IDH-wildtype gliomas, and down-regulated in IDH-wildtype glioma lines. MiR-16-5p overexpression reduced expression of important cell cycle and apoptosis regulators in glioma cells, including CDK6, CDC25A, CCND3, CCNE1, WEE1, CHEK1, BCL2 and MCL1. In line, CDK6, WEE1, CHEK1, BCL2 and MCL1 transcript levels were increased in WHO grade III or IV gliomas. TSA treatment and HDAC3 knockdown in glioma cells induced miR-16-5p up-regulation and reduced expression of its targets. Moreover, miR-16-5p overexpression inhibited proliferation and induced apoptosis in various glioma cell lines and increased sensitivity of A172 glioma cells to irradiation and TMZ. CONCLUSION: Reduced expression of miR-16-5p contributes to glioma cell proliferation, survival and resistance to cytotoxic therapy.

Virtual Reality Therapy in Palliative Care: A Case Series.

OBJECTIVES: Virtual reality (VR) opens a variety of therapeutic options to improve symptom burden in patients with advanced disease. Until to date, only few studies have evaluated the use of VR therapy in the context of palliative care. This case series aims to evaluate the feasibility and acceptability of VR therapy in a population of palliative care patients. METHODS: In this single-site case series, we report on six palliative care patients undergoing VR therapy. The VR therapy consisted of a one-time session ranging between 20 to 60 minutes depending on the patient's needs and the content chosen for the VR sessions. A semi-structured survey was conducted and the Edmonton Symptom Assessment System (ESAS) and the Distress Thermometer were performed pre- and post-intervention. RESULTS: Overall, VR therapy was well accepted by all patients. Five out of six patients reported having appreciated VR therapy. There were individual differences of perceived effects using VR therapy. The semi-structured survey revealed that some patients felt a temporary detachment from their body and that patients were able to experience the VR session as a break from omnipresent worries and the hospital environment ("I completely forgot where I am"). There was a considerable reduction in the total ESAS score post-treatment (T0 ESASTot = 27.2; T1 ESASTot = 18.8) and a slightly reduction in distress (T0 DTTot = 4.4; T1 DTTot = 3.8). However, two patients were more tired after the intervention.Significance of Results: Our preliminary results demonstrate that VR therapy is acceptable, feasible and safe for use within a palliative care population and appears to be a viable treatment option. Clinical trials are both warranted and necessary to confirm any therapeutic effects of VR therapy, as is the need to tailor VR systems better for use in palliative care settings.

Histochemistry of otic capsule sclerotic lesions in Palmerston North autoimmune strain mice.

Otic capsule osteogenesis is a common finding in temporal bones from autoimmune disease individuals. However, the underlying cellular mechanisms are poorly understood. Therefore, to better understand this relationship of autoimmune disease and otic capsule pathology, inner ear sclerotic lesions of the Palmerston North autoimmune disease mouse were histochemically stained to identify their content and potential osteogenic processes. Lesions stained positive for calcium, amyloid, fibrinoid, and glycoproteins (PAS), but negative for collagen, calcium oxalate, reticular fibers and glycosaminoglycans (Alcian Blue). Amyloid and fibrinoid deposition are associated with other immune disease, which suggests these local processes may provide a protein substructure that calcifies in lesion progression. Similar cellular mechanisms may underlie certain types or phases of human autoimmune otic capsule disease.

Replantation of the amputated nose.

OBJECTIVE: To assess the effectiveness of replantation in the treatment of nasal amputations. DESIGN: Retrospective chart review. SETTING: A university medical center. RESULTS: In no case did the replant survive completely, and in all cases revision surgery was required. However, in all cases, the resulting deformity was less than the original defect. In our pediatric patients, reconstruction with cartilage grafting and a midline forehead flap was successful and demonstrated proportionate and appropriate growth. CONCLUSIONS: It is our belief that replantation serves many therapeutic functions. At the very least, there is the psychological/emotional factor that is involved in attempting to replace a native body part that has been severed. Also, it is difficult to persuade parents and patients that the amputated tissue that has been handled with kid gloves by paramedics, maintaining its pink "alive" color, is ultimately doomed to failure. Forehead flaps and conchal cartilage grafts are more willingly accepted after a "failed" replantation than as primary reconstructions. In every instance, we believe, the ultimate defect will be smaller than the original deformity. Certainly, the need for vestibular lining reconstruction is far less. Thus, the ultimate healed defect from the replantation greatly facilitates final nasal reconstruction.

Otic capsule bony lesions in the Palmerston North autoimmune mouse.

Otosclerosis is an otic capsule disorder of unknown etiology. While autoimmunity has been proposed as part of the etiopathogenesis of otosclerosis, no spontaneous autoimmune disease animal model has been identified. In the Palmerston North mouse, a model for systemic lupus erythematosus, sclerotic lesions consistently develop within the modiolus that are correlated with systemic autoimmune disease symptoms. No lesions were seen in 2-month-old mice, which is before autoimmune disease onset at 4 months. Lesions were first seen in mice at 6 to 8 months of age and increased in size and frequency thereafter. By 20 months, all ears examined had the otic capsule lesions, which were primarily perivascular in location and composed of both noncellular and cellular elements. The noncellular material was globular to fibrillar in arrangement and stained positively for calcium. The associated cells appeared to be metabolically active fibroblasts. It is proposed that the Palmerston North mouse may serve as a model to further investigate the role of autoimmunity in otosclerosis and other forms of otic capsule osteogenesis.

Aneurysm of the facial vein.

Venous aneurysms of the head and neck are rare lesions that present as soft, compressible, nonpulsatile masses with no associated bruit. A case of a facial vein aneurysm is reported along with a discussion of differential diagnosis, evaluation, and treatment.

Relocation of the 1936 Mojokerto skull discovery site near Perning, East Java.

The fossil calvaria known as the Mojokerto child's skull was discovered in 1936, but uncertainties have persisted about its paleoenvironmental context and geological age because of difficulties in relocating the discovery site. Past relocation efforts were hindered by inaccuracies in old base maps, intensive post-1930s agricultural terracing, and new tree and brush growth. Fortunately geologic cross sections and site photographs from 1936-1938-not fully utilized in past relocation fieldwork-closely circumscribe site geography and geology. These documents match the conditions at just one sandstone outcrop. It is situated on the southern margin of a topographic nose at the upper end of a approximately 18 m-wide gully ( approximately 0663760 m E, 9183430 m N, UTM Zone 49 M), approximately 15 m southeast of the Kumai et al. (1985) relocation. The relocated discovery bed is approximately 3.3 m of fossiliferous pebbly sandstone, a river-channel deposit cut into tuffaceous mudstone. The sandstone and mudstone beds correspond to original site descriptions. Pebbly sandstone is also found within the skull. The calvaria is well-preserved and taphonomically similar to large and fragile specimens found among several hundred vertebrate fossils excavated from the sandstone in 2001-2002. Since no well-preserved fossils were found intact at the surface of the sandstone, the good condition of the Mojokerto skull suggests that it was buried fully when discovered. The relocated hominin bed is the uppermost fluvial sandstone of a marine-deltaic sequence in the upper Pucangan Formation. The Mojokerto child probably died along the ancient seacoast, judging from the large extent of the deltaic facies and evidence that the calvaria experienced minimal transport. The relocated discovery bed is approximately 20 m stratigraphically above the horizon from which the widely cited 1.81+/-0.04 Ma (40)Ar/(39)Ar date for the skull was obtained. Additional field and laboratory results will be required to determine the skull's age.